and ( + ) -( Z ) +A + F + C -(-)-(E) are consistent with the solvent effect on kb. Structure D either as a transition state or intermediate might provide less charge separation than F, and could be used to explain why k , > kb. A rapidly reversible D e E stage is equally attractive. In effect, inclusion of such stages in epimerization at cyanoacetate provides a path for a conducted tour of C+ of benzyl from C-to 0-, to inverted C-, to product inverted at the cyanoacetate center, and resembles ionic conducted tour mechanisms suggested in other connections.6 Intervention of intermediates G, H, and J in the epimerization at the cyanoacetate center in D M F also might explain k , > kb in this medium. No such structures are available for epimerization at the benzyl center. Racemization rates appear equally sensitive to solvent character, and probably the same intermediates are involved as in the two epimerization reactions. For example, (+)-(Z) + A + B or Cenantiomer of A + (-)-(Z) are the simplest processes.(6) (a) D.peratures and the more polar solvent favor larger spreads in rates of the three reactions. In DMF, in going from 100 to 126O, k,/kb decreased by 3.3 for a 26" temperature rise. Extrapolation to 175' gives only a factor of 2.7, not far from benzene at 175" (1.6). Possibly temperature differences are mainly responsible for changes in k,/kb, not solvent polarity or nucleophilicity.Mechanisms of the three reactions might involve intermediates A-J. Of these only E is not an ion pair.5 Mechanism ( + ) -( Z ) + E+ (+)-(E) is incompatible with the dramatic and similar response of k, and kb to solvent polarity. Epimerization at benzyl (kb) cannot involve E as an intermediate. Mechanismsdefinitely are compatible with the solvent effects and nonaccumulation of E only if k-1 >> kl > kz.This scheme would make fortuitous the similar response of k , and kb to solvent polarity. An analogous mechanism for the I $ E + D or G stages was found not to occur in methanol,2a although k, and k (methanolysis) are not far from one another in value. These facts make such a scheme highly improbable. Mechanisms that involve G, H, and J are not possible in benzene, and yet epimerization occurs. A B E F G H D Mechanisms (+)-(Z) -A -B --t (+)-(E), (+)-( Z ) -A -D -B -(+)-(E), and (+)-(Z) + A ---t D E -B + (+)-(E), with the first stage rate determining, are consistent with the solvent effect on k,. Mechanisms ( 5 ) Intervention of ketene acetal in (+)-(Z)-I -(+)++I would nicely correlate this particular epimerization reaction with the wellknown aldehydo or acylcyclopropane * dihydrofuran rearrangement Sir:The use of o-nitrobenzyl derivatives as photosensitive blocking reagents for amino and carboxyl functions in peptides has beenIn this communication we describe some new photosensitive blocking groups, and conditions required for achieving photoremoval in quantitative yields.Amino acid derivatives, in which the amino function was blocked with photosensitive protecting groups of two kinds, namely, 6-nitroveratryloxycarbonyl (NVOC) and 2-n...

Methionine residues in peptides and proteins were oxidized to methionine sulfoxides by mild oxidizing reagents such as chloramine-T and N-chlorosuccinimide at neutral and slightly alkaline pH. With chloramine-T cysteine was also oxidized to cystine but no other amino acid was modified; with N-chlorosuccinimide tryptophans were oxidized as well. In peptides and denaturated proteins all methionine residues were quantitatively oxidized, while in native proteins only exposed methionine residues could be modified. Extent of oxidation of methionine residues was determined by quantitative modification of the unoxidized methionine residues with cyanogen bromide (while methionine sulfoxide residues remained intact), followed by acid hydrolysis and amino acid analysis. Methionine was determined as homoserine and methionine sulfoxide was reduced back to methionine. Sites of oxidation were identified in a similar way by cleaving the unoxidized methionyl peptide bonds with cyanogen bromide, followed by quantitative end-group analysis of the new amino-terminal amino acids (by an automatic sequencer).

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4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure-activity relationships at various positions of the dihydropyridine ring (the 3- and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed synthetically. Using the combined protection of the 1-ethoxymethyl and the 5-[2-(trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5-position allowing various substitutions. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A2A receptors. Structure-activity analysis at adenosine receptors indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position resulted in, at most, only moderate selectivity for A3 adenosine receptors. Ring substitution (e.g., 4-nitro) of the 4-phenylethylnyl group did not provide enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At the 3-position of the dihydropyridine ring, esters were much more selective for A3 receptors than closely related thioester, amide, and ketone derivatives. A cyclic 3-keto derivative was 5-fold more potent at A3 receptors than a related open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters and a series of substituted benzyl esters were prepared and tested. (Trifluoromethyl)-, nitro-, and other benzyl esters substituted with electron-withdrawing groups were specific for A3 receptors with nanomolar Ki values and selectivity as high as 37000-fold. A functionalized congener bearing an [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the synthesis of biologically active conjugates.